11-47260229-T-C

Position:

• chr11-47260229-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005693.4(NR1H3):​c.233-180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,018 control chromosomes in the GnomAD database, including 11,798 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11798 hom., cov: 32)
• Consequence: NR1H3 NM_005693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H3	NM_005693.4	c.233-180T>C		intron_variant		ENST00000441012.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H3	ENST00000441012.7	c.233-180T>C		intron_variant		1	NM_005693.4	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57426 AN: 151900 Hom.: 11799 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57448 AN: 152018 Hom.: 11798 Cov.: 32 AF XY: 0.388 AC XY: 28849 AN XY: 74320

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.324

Alfa AF: 0.339 Hom.: 1158

Bravo AF: 0.375

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2279239; hg19: chr11-47281780;